搅拌对红霉素发酵的影响

在20t工业发酵罐中,研究了涡轮桨和翼形轴流桨搅拌对红霉素发酵过程的影响,重点考察了粘度、溶氧、效价、搅拌电流和糖代谢等过程参数的变化,以及搅拌功耗与发酵产量之间的关系。研究结果表明：(1)不同的搅拌桨搅拌其发酵过程参数(粘度,溶氧,效价等)随时间的变化曲线有明显的差异;(2)搅拌功耗同发酵产量之间的关系,翼形桨明显不同于涡轮桨;(3)在相同的生产条件下,用翼形桨代替涡轮桨可节省搅拌功耗。     

红霉素发酵工艺优化研究

通过摇瓶正交实验,得出7种营养成分对红霉素生物合成的影响程度,对发酵工艺条件进行了优化研究,找到了红色链霉菌抗噬菌体68#菌种生长的优化组合,得出快速碳源(葡萄糖)与慢速碳源(淀粉)配比为2.64时,有利于红霉素的生物合成。还原糖/氮为20,总糖/氮为80～120时对红霉素发酵极为有利。借助磷酸三钙、沸石对NH+的独特吸附和释放作用,将二者按5∶1混合配成吸附和吐纳效果很好的捕集剂,对发酵液中游离无机氮源进行控制,可使抗生素生物合成提高15%～29%。     

稀土元素对红霉素发酵的影响

通过对红霉素发酵培养基中添加稀土元素的研究,确定了几种能对发酵效价有提高作用的稀土元素及其浓度,当其中镧La^3＋、钕Nd^3＋和铈Ce^4＋离子浓度分别为50mg／L、50mg/L和100mg／L时对提高红霉素效价水平最显著,提高了32％、25％和25％,并且对改善红霉素组分也有明显作用,红霉素A组分相对百分含量分别提高18．9％、32．7％和34．4％,红霉素B组分分别减少24．1％、58．6％和62．1％。     

污染细菌对红霉素发酵的影响

木文考查了两种常见污染细菌对红霉素发酵的影响。发现枯草芽孢杆菌污染后迅速引起总糖和还原糖的大量消耗,且在早期就已完全抑制了红霉素的生成;另一种微球菌虽也使发酵过程中的糖耗明显增加,但对红霉素的影响较小,红霉素的合成一直持续到发酵终了。     

乳杆菌在发酵乳饮料中的应用

为了制备更优质的乳酸菌饮料,本论文主要以鼠李糖乳杆菌、瑞士乳杆菌、副干酪乳杆菌、嗜酸乳杆菌四种典型的乳酸杆菌为研究菌种,详细分析它们在乳品发酵过程中pH、酸度变化,货架期内的活菌数变化以及代谢产生的有机酸种类和耐胃酸的能力,以确定乳杆菌在乳饮料中应用的最优条件,分析其应用于乳饮料中的可行性。本文为乳杆菌在乳饮料中的应用提供了参考依据。     

高粘发酵体系不同搅拌桨的CFD模拟及发酵验证

搅拌桨是高好氧高黏度微生物发酵实现高效反应必不可少的因素之一,不同搅拌桨组合对发酵过程的影响十分重要。威兰胶是由产碱杆菌在高耗氧高粘度发酵体系下合成的胞外微生物多糖,广泛应用于水泥、石油、油墨、食品等行业中。本研究借助于计算流体力学(Computational fluid dynamics,CFD)的方法,以威兰胶发酵液体系为研究体系,研究了6种不同搅拌桨组合在反应器内流体速率分布、剪切速率、和气含率等参数。将模拟效果较好的3种组合用于威兰胶发酵过程。研究表明MB-4-6搅拌桨组合对改善发酵罐内部的溶氧及流场分布效果最明显,威兰胶产量水平提高了13%。同时在该组合下威兰胶的产品粘度得到有效提高。     

聚类分析在黄霉素发酵过程中的应用

【目的】将聚类分析的方法应用于黄霉素摇瓶发酵条件的优化过程中。【方法】通过系统聚类算法、K均值聚类算法和模糊C均值聚类算法对不同批次黄霉素发酵的摇瓶数据的聚类分析进行比较,发现模糊C均值聚类算法优于其他聚类算法,确定了以模糊C均值聚类算法对黄霉素摇瓶发酵数据进行聚类分析。【结果】然后利用模糊C均值聚类算法选取优质组样本,并利用优质样本优化了黄霉素摇瓶发酵的控制参数分布范围。【结论】这充分证明了聚类分析在发酵过程的优化过程中有良好的实用性。     

现代生物技术在中药发酵中的应用

发酵是中药炮制一个重要的方面,近年来关于运用现代生物技术来发酵中药的研究越来越多。本文阐述了现代中药发酵的意义、区别传统发酵的优势以及现阶段的发展概况。     

Knocking out of tailoring genes eryK and eryG in an industrial erythromycin-producing strain of Saccharopolyspora erythraea leading to overproduction of erythromycin B, C and D at different conversion ratios

Aims: To overproduce erythromycin C, B or D and evaluate the effect of disruption of tailoring genes eryK and eryG in an industrial erythromycin producer. Methods and Results: The tailoring genes eryG and eryK were inactivated individually or simultaneously by targeted gene disruption in an industrial strain Saccharopolyspora erythraea HL3168 E3, resulting in the overproduction of erythromycin C (2·48 g l^?1), B (1·70 g l^?1) or D (2·15 g l^?1) in the mutant strain QL‐G, QL‐K or QL‐KG, respectively. Analysis of the erythromycin congeners throughout the fermentation indicated that, at the end of fermentation, comparatively large amount of erythromycin D (0·67 g l^?1) was accumulated in QL‐G, whereas only small amount of erythromycin D (0·10 g l^?1) was produced in QL‐K. Conclusions: Inactivation of tailoring genes eryG and eryK in the high producer did not affect the biosynthesis of erythromycin. However, erythromycin D could be more efficiently methylated by EryG than be hydroxylated by EryK. Significance and Impact of the Study: Development of the mutant strains provides a method for the economical large‐scale production of potent lead compounds. The information about the accumulation and conversion of erythromycins in the industrial strains may contribute to further improving erythromycin production.     

Microarray analysis of erythromycin resistance determinants

AIMS: To develop a DNA microarray for analysis of genes encoding resistance determinants to erythromycin and the related macrolide, lincosamide and streptogramin B (MLS) compounds. METHODS AND RESULTS: We developed an oligonucleotide microarray containing seven oligonucleotide probes (oligoprobes) for each of the six genes (ermA, ermB, ermC, ereA, ereB and msrA/B) that account for more than 98% of MLS resistance in Staphylococcus aureus clinical isolates. The microarray was used to test reference and clinical S. aureus and Streptococcus pyrogenes strains. Target genes from clinical strains were amplified and fluorescently labelled using multiplex PCR target amplification. The microarray assay correctly identified the MLS resistance genes in the reference strains and clinical isolates of S. aureus, and the results were confirmed by direct DNA sequence analysis. Of 18 S. aureus clinical strains tested, 11 isolates carry MLS determinants. One gene (ermC) was found in all 11 clinical isolates tested, and two others, ermA and msrA/B, were found in five or more isolates. Indeed, eight (72%) of 11 clinical isolate strains contained two or three MLS resistance genes, in one of the three combinations (ermA with ermC, ermC with msrA/B, ermA with ermC and msrA/B). CONCLUSIONS: Oligonucleotide microarray can detect and identify the six MLS resistance determinants analysed in this study. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results suggest that microarray-based detection of microbial antibiotic resistance genes might be a useful tool for identifying antibiotic resistance determinants in a wide range of bacterial strains, given the high homology among microbial MLS resistance genes.     

L22 ribosomal protein and effect of its mutation on ribosome resistance to erythromycin

The ribosomal protein L22 is a core protein of the large ribosomal subunit interacting with all domains of the 23S rRNA. The triplet Met82-Lys83-Arg84 deletion in L22 from Escherichia coli renders cells resistant to erythromycin which is known as an inhibitor of the nascent peptide chain elongation. The crystal structure of the Thermus thermophilus L22 mutant with equivalent triplet Leu82-Lys83-Arg84 deletion has been determined at 1.8A resolution. The superpositions of the mutant and the wild-type L22 structures within the 50S subunits from Haloarcula marismortui and Deinococcus radiodurans show that the mutant beta-hairpin is bent inward the ribosome tunnel modifying the shape of its narrowest part and affecting the interaction between L22 and 23S rRNA. 23S rRNA nucleotides of domain V participating in erythromycin binding are located on the opposite sides of the tunnel and are brought to those positions by the interaction of the 23S rRNA with the L22 beta-hairpin. The mutation in the L22 beta-hairpin affects the orientation and distances between those nucleotides. This destabilizes the erythromycin-binding "pocket" formed by 23S rRNA nucleotides exposed at the tunnel surface. It seems that erythromycin, while still being able to interact with one side of the tunnel but not reaching the other, is therefore unable to block the polypeptide growth in the drug-resistant ribosome.     

Cloning and sequencing of a plasmid-mediated erythromycin resistance determinant from Staphylococcus xylosus

A 2.3-kb DNA fragment cloned from plasmid pCH200, the largest (52 kb) of four plasmids detected in Staphylococcus xylosus, was found to confer resistance to 14-membered ring macrolides in Bacillus subtilis and Staphylococcus aureus. DNA-sequence analysis of the fragment revealed the presence of an open-reading frame, the deduced product of which was identical to one of the two ATP-binding domains encoded by the macrolide/streptogramin-B-resistance gene msrA of Staphylococcus epidermidis. The observation that a polypeptide homologous to the C-terminus of MsrA is capable of mediating erythromycin resistance in the absence of the N-terminal region is of significance both to the evolution and functional activity of members of the ATP-binding transport super-gene family.     

蛋白质组学技术在工业发酵梭菌研究中的应用

介绍了目前应用较广泛的蛋白质组学技术的原理、应用及优缺点;总结了发酵工业中常用的梭菌属细菌;重点阐述了蛋白质组学技术在工业发酵梭状芽孢杆菌研究中的应用,为工业发酵菌种的改良和发酵工艺的优化提供理论依据。最后讨论了今后工业发酵菌种蛋白质组学研究的重点和方向。     

Effects of penicillin and erythromycin on adherence of invasive and noninvasive isolates of Streptococcus pyogenes to laminin

This study investigated the possible relationship between the invasiveness of group AStreptococcus (GAS) strains and their abilities to adhere tolaminin and assessed the effects of subinhibitory concentrations of penicillin anderythromycin on the ability of GAS to adhere to laminin. The adherence of noninvasiveand highly invasive isolates of GAS to laminin was significantly higher than theadherence displayed by isolates of low invasiveness. Antibiotic treatment causedsignificant reductions in adherence to laminin in all three groups of strains.Penicillin was more successful in reducing the adherence abilities of the tested GASstrains than erythromycin.     

补料发酵工艺的应用及其研究进展

综述了补料工艺在发酵工业中应用和研究。介绍了补料发酵工艺及其优点,着重讨论了补料发酵动力学和控制理论研究,以期为补料发酵的应用提供充分的参考依据。     

Application of gravitational sedimentation to efficient cellular recycling in continuous alcoholic fermentation

A mathematical model for the sedimentation velocity in an inclined parallel plate sedimenter is proposed. The parameters of the alcoholic fermentation broth (cell density of Saccharomyces cerevisiae, density of the fermentation medium, viscosity of the broth at various alcohol and biomass contents) were determined experimentally. The sedimentation velocities were predicted under the various operational conditions and parameters, both of the broth (the alcohol concentration and cell content) and the sedimenter prototype (length, distance between the plates, and slope). The proposed model for the sedimentation velocity presented a good correlation with the experimental results of continuous sedimentation. These sedimenter prototypes were assembled and tested for efficiency of separation of yeast cell under conditions considered for interest for continuous alcoholic fermentation. A selective filter for the overflow composed of calcium alginate gel improved operation. A high operational stability, high separation efficiency (over 98%), and adequate settler residence times (about 20 min) were attained. The operational results permitted the operation of continuous alcoholic fermentation with cellular recycling effected exclusively by gravitational sedimentation, this characterizing a process of enormous industrial interest because of the operational simplicity and low operational and maintenance costs. (c) 1993 John Wiley & Sons, Inc.